Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit...

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Help with Help with Hepatology Hepatology Spire 2013 Spire 2013 Dr Allister J Grant Dr Allister J Grant Consultant Hepatologist Consultant Hepatologist Leicester Liver Unit Leicester Liver Unit University Hospitals Leicester NHS University Hospitals Leicester NHS Trust Trust

Transcript of Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit...

Page 1: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Help with HepatologyHelp with Hepatology

Spire 2013Spire 2013

Dr Allister J GrantDr Allister J GrantConsultant HepatologistConsultant Hepatologist

Leicester Liver UnitLeicester Liver UnitUniversity Hospitals Leicester NHS TrustUniversity Hospitals Leicester NHS Trust

Page 2: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Abnormal LFT’s in well patientsAbnormal LFT’s in well patients

1)1) Isolated raise in bilirubinIsolated raise in bilirubin

2)2) γGT raisedγGT raised

1)1) ALT rise predominant ALT rise predominant

2)2) ALP rise predominantALP rise predominant

Page 3: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

1) Isolated raise in bilirubin1) Isolated raise in bilirubin

DifferentialDifferential Gilberts vs HaemolysisGilberts vs Haemolysis

Gilberts- Gilberts- unconjugated hyperbilirubinaemiaunconjugated hyperbilirubinaemia

Haemolysis-Haemolysis-Unconjugated hyperbilirubinaemiaUnconjugated hyperbilirubinaemia

splenomegaly, anaemia , splenomegaly, anaemia , DCT, haptoglobin, reticulocyte count, filmDCT, haptoglobin, reticulocyte count, film

Page 4: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

2) 2) -Glutamyl transpeptidase-Glutamyl transpeptidase

The high sensitivity and very low specificity seriously The high sensitivity and very low specificity seriously hampers the usefulness of this testhampers the usefulness of this test

If ALP is elevated and GGT is elevated then the raise in If ALP is elevated and GGT is elevated then the raise in ALP is likely to be hepatic in originALP is likely to be hepatic in origin

Elevated in Elevated in a whole host of liver diseasesa whole host of liver diseases Drugs/AlcoholDrugs/Alcohol Obesity/ dyslipidaemia/ DMObesity/ dyslipidaemia/ DM CCFCCF Kidney, Pancreas, ProstateKidney, Pancreas, Prostate

Page 5: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

The majority of abnormal LFTs in The majority of abnormal LFTs in asymptomatic people occur in those with:asymptomatic people occur in those with:

Diabetes or metabolic syndrome Diabetes or metabolic syndrome (increased risk of NAFLD) (increased risk of NAFLD)

Excessive alcohol intake Excessive alcohol intake Chronic hepatitis B Chronic hepatitis B Chronic hepatitis C Chronic hepatitis C DrugsDrugs

2) ALT rise predominant2) ALT rise predominant2) ALT rise predominant2) ALT rise predominant

Page 6: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Case - Case - Mr ZMr Z

59y Architect59y Architect

Type 2 DM 15 yrs on diet aloneType 2 DM 15 yrs on diet aloneBMI 35BMI 35HypertensionHypertension

Amlodipine , RamiprilAmlodipine , Ramipril

Minimal AlcoholMinimal Alcohol

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Mr RPMr RP

Generally unwell for 2 yearsGenerally unwell for 2 years CytopaeniaCytopaenia

Low Hb/plateletsLow Hb/platelets Normal haematological Ix (peripheral Normal haematological Ix (peripheral

consumption)consumption)

May 07May 07 LGH admission with ataxia/drowsinessLGH admission with ataxia/drowsiness Extensive IxExtensive Ix

Page 8: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Mr RPMr RP

CT abdoCT abdo cirrhotic liver, portal hypertension, splenomegalycirrhotic liver, portal hypertension, splenomegaly

OPD referralOPD referral Alb 28, Pl 65 LFT’s normal, INR 1.5Alb 28, Pl 65 LFT’s normal, INR 1.5 Imaging compatible with cirrhosisImaging compatible with cirrhosis Reversal of sleep pattern, lack of concentrationReversal of sleep pattern, lack of concentration Daytime somnelence, intermittant confusionDaytime somnelence, intermittant confusion OGD- varicesOGD- varices

Page 9: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

How common is NAFLD?How common is NAFLD?How common is NAFLD?How common is NAFLD?

The most common cause of abnormal liver function The most common cause of abnormal liver function tests in the United States.tests in the United States.

Estimated 30.1 million with NAFLD and 8.6 million Estimated 30.1 million with NAFLD and 8.6 million with NASHwith NASH

Affects 10-24% of the populationAffects 10-24% of the population 58-74% of the obese population58-74% of the obese population Affects 2.6% of childrenAffects 2.6% of children 23-53% of obese children23-53% of obese children

Page 10: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

LEICEST

ER

Page 11: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

SteatosisSteatosis

SteatohepatitisSteatohepatitis

CirrhosisCirrhosis

Hepatocellular carcinoma

Hepatocellular carcinoma

Non Alcoholic Fatty Liver Disease (NAFLD)Spectrum of Hepatic Pathology

Non Alcoholic Fatty Liver Disease (NAFLD)Spectrum of Hepatic Pathology

Page 12: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.
Page 13: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Diseases Associated with SteatohepatitisDiseases Associated with Steatohepatitis

1.Alcoholism1.Alcoholism2.Insulin resistance2.Insulin resistance a.Metabolic Syndromea.Metabolic Syndrome

i.Obesityi.Obesityii.Diabetesii.Diabetesiii.Hypertriglyceridemiaiii.Hypertriglyceridemiaiv.Hypertensioniv.Hypertension

b.Lipoatrophyb.Lipoatrophy c.Mauriac Syndromec.Mauriac Syndrome d.PCOSd.PCOS3.Disorders of lipid metabolism3.Disorders of lipid metabolism a.Abetalipoproteinemiaa.Abetalipoproteinemia b.Hypobetalipoproteinemiab.Hypobetalipoproteinemia c.Andersen’s diseasec.Andersen’s disease d.Weber-Christian syndromed.Weber-Christian syndrome4.Total parenteral nutrition4.Total parenteral nutrition5. HCV 5. HCV (certain genotypes)(certain genotypes)6. Untreated coeliac disease6. Untreated coeliac disease

7.Severe weight loss7.Severe weight loss a.Jejuno-ileal bypassa.Jejuno-ileal bypass b.Gastric bypassb.Gastric bypass c.Severe starvationc.Severe starvation8.Iatrogenic8.Iatrogenic a.Amiodaronea.Amiodarone b.Diltiazemb.Diltiazem c.Tamoxifenc.Tamoxifen d.Steroidsd.Steroids e.HAARTe.HAART f. tetracyclinef. tetracycline g.glucosamineg.glucosamine9.Refeeding syndrome9.Refeeding syndrome10.Exposure to toxic agents10.Exposure to toxic agents a.Environmenta.Environment b.Workplace – Sb,Th,Bab.Workplace – Sb,Th,Ba

Page 14: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

NASHNASH

Affects 3.5-5% of the populationAffects 3.5-5% of the population

The rates of progression to cirrhosis have been The rates of progression to cirrhosis have been estimated at between 5% and 20% over 10 years.estimated at between 5% and 20% over 10 years.

There aren't any non-invasive means of predicting which There aren't any non-invasive means of predicting which patients are at risk of progression, and there are no patients are at risk of progression, and there are no agreed guidelines on how to monitor progression.agreed guidelines on how to monitor progression.

Page 15: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Natural historyNatural historyNatural historyNatural history

Simple steatosis: relatively benign “liver” prognosis with Simple steatosis: relatively benign “liver” prognosis with a risk of developing clinical evidence of cirrhosis over a risk of developing clinical evidence of cirrhosis over 15–20 years in the order of 1%–2%.15–20 years in the order of 1%–2%.

NASH and fibrosis: risk of progress to cirrhosis between NASH and fibrosis: risk of progress to cirrhosis between 0% at 5 years to 12% over 8 years. 0% at 5 years to 12% over 8 years.

Cirrhotic: high risk of developing hepatic Cirrhotic: high risk of developing hepatic decompensation and of dying from a liver-related cause decompensation and of dying from a liver-related cause including HCC.including HCC.

Page 16: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Initial InvestigationInitial Investigation

Look for risk factorsLook for risk factors BMI, DM, HBP, Lipids,FHx, Drugs, AlcoholBMI, DM, HBP, Lipids,FHx, Drugs, Alcohol

Liver screen (to exclude other diseases)Liver screen (to exclude other diseases) Including Glc/GTT/HbA1c/Lipids/ASTIncluding Glc/GTT/HbA1c/Lipids/AST Pl, Alb, INRPl, Alb, INR

USSUSS Spleen size, fatty liver, collateralsSpleen size, fatty liver, collaterals

Page 17: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Fibroscan® Fibroscan® Electronic platformElectronic platform

Ultrasonic signals acquisitionUltrasonic signals acquisition Numerical signal processingNumerical signal processing

Integrated computerIntegrated computer Stiffness measurementStiffness measurement Examinations databaseExaminations database

Dedicated probes with unique Dedicated probes with unique technologytechnology

Vibrator (50 Hz)US Transducer

(3,5 MHz)

Fibroscan® (Echosens, Paris, France)

Page 18: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Position of probe & explored volumePosition of probe & explored volume

Cylinder of 1 cm wide & 4 cm long

From 25 mm to 65 mm below skin surface

This volume is at least 100 times bigger than a biopsy sample

Page 19: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Results

Stiffness (kPa)

Median value of 10 shots

3.9 Kilo Pascals

At least 10 shots

Success Rate: ≥ 60%

IQR * (kPa)

Interval around median

Contains 50% of valid shots

≤ 25% of median value

Page 20: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.
Page 21: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

NASH ManagementNASH Management

  1) 1) All patientsAll patients should be encouraged to exercise, as there is good evidence should be encouraged to exercise, as there is good evidence that even in the absence of weight loss exercise improves NASH.that even in the absence of weight loss exercise improves NASH.

Obese PatientsObese PatientsWeight reducing diet (aim for 10%, 1-2lb per week)Weight reducing diet (aim for 10%, 1-2lb per week)In patients with BMI>28 with risk factors, or >30 without risk factors, In patients with BMI>28 with risk factors, or >30 without risk factors, consider treatment with Orlistat etc.consider treatment with Orlistat etc.

2) 2) Diabetic PatientsDiabetic PatientsGood diabetic control (HbA1c <6.5%) Good diabetic control (HbA1c <6.5%) Metformin Metformin ThiazolidinedionesThiazolidinedionesDietician for re-education.Dietician for re-education.Diabetologist if glucose control is difficult. Diabetologist if glucose control is difficult. 

Page 22: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

NASH ManagementNASH Management

3) 3) Patients with Hyperlipidaemia and abnormal LFT’sPatients with Hyperlipidaemia and abnormal LFT’s

Dyslipidaemia should be aggressively addressedDyslipidaemia should be aggressively addressed

Dietician ReviewDietician Review

Hypercholesterolaemia -Statins Hypercholesterolaemia -Statins

Hypertriglycerideaemia -Fibrate. Hypertriglycerideaemia -Fibrate.

Lipid ClinicLipid Clinic

   Avoid DrugsAvoid Drugs

amiodarone, glucocorticoids, methotrexate, nifedipine, synthetic amiodarone, glucocorticoids, methotrexate, nifedipine, synthetic estrogens, tamoxifenestrogens, tamoxifen

Antioxidants?Antioxidants?

Page 23: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Alcohol Related Deaths Alcohol Related Deaths E&W 1979-2010E&W 1979-2010

http://www.statistics.gov.uk/cci/nugget.asp?id=1091

Page 24: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Mon

thly

adm

issi

on r

ate

UHL Alcohol Admissions 2004-8UHL Alcohol Admissions 2004-8

Page 25: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Spectrum of Alcoholic Liver DiseaseSpectrum of Alcoholic Liver Disease

The most common manifestations of alcoholic The most common manifestations of alcoholic liver disease are:liver disease are:

Alcoholic steato-hepatitisAlcoholic steato-hepatitis Acute alcoholic hepatitisAcute alcoholic hepatitis Cirrhosis due to alcoholCirrhosis due to alcohol

Page 26: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Alcoholic HepatitisAlcoholic Hepatitis

Most florid manifestation of ALDMost florid manifestation of ALD Cholestatic liver disease associated with the long term Cholestatic liver disease associated with the long term

heavy use of alcoholheavy use of alcohol Often a precursor to the development of cirrhosisOften a precursor to the development of cirrhosis More severe forms are associated with a high mortalityMore severe forms are associated with a high mortality 1yr mortality after initial hospitalisation is 40%1yr mortality after initial hospitalisation is 40%

Best treatmentBest treatment Stop drinkingStop drinking Resolution occurs within weeks-months +/- cirrhosisResolution occurs within weeks-months +/- cirrhosis

Page 27: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

SymptomsSymptoms

FeverFever HepatomegalyHepatomegaly JaundiceJaundice CoagulopathyCoagulopathy Features of hepatic decompensationFeatures of hepatic decompensation

However, milder forms of alcoholic hepatitis However, milder forms of alcoholic hepatitis often do not cause any symptomsoften do not cause any symptoms

Page 28: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

InvestigationInvestigation

BiochemistryBiochemistry AST/ALT ratio >1.5AST/ALT ratio >1.5 ALT usually <100 IU/mlALT usually <100 IU/ml Raised Raised GT (variable)GT (variable) Raised ALP (variable)Raised ALP (variable) Low Albumin (advanced Low Albumin (advanced

disease)disease)

Bilirubin (≥80 mmol/l)Bilirubin (≥80 mmol/l)

HaematologyHaematology Prolonged INR Prolonged INR

(advanced disease)(advanced disease) Macrocytosis / Macrocytosis /

anaemiaanaemia LeukocytosisLeukocytosis Thrombocytopenia Thrombocytopenia

(advanced disease)(advanced disease)

Page 29: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Glasgow Alcoholic Hepatitis ScoreGlasgow Alcoholic Hepatitis Score

Age <50 ≥ 50

WCC(109/l) <15 ≥15

Urea (mmol/l)<5 ≥5

PT ratio <1.5 1.5-2.0 >2.0

Bili (mol/l) <125 125-250 >250

Score 1 2 3

Patients score from 5-12 points.

Score >8 was used to define the high risk population and maximised sensitivity and specificity.

Page 30: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Survival from Alcoholic HepatitisSurvival from Alcoholic Hepatitis

28 day survival (%) 84 day survival(%)Day 1

GAHS <9 87 79 GAHS ≥9 46 40

Day 7

GAHS<9 93 86GAHS ≥9 47 37

Derivation and validation datasets combined – 436 patients

Page 31: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

CorticosteroidsCorticosteroids

If the patient has severe alcoholic hepatitis If the patient has severe alcoholic hepatitis mDF>32, MELD >11, GAHS>8mDF>32, MELD >11, GAHS>8

Therapeutic trial of prednisolone 40mg POTherapeutic trial of prednisolone 40mg PO

7 days7 days

If no improvement in bilirubin then discontinueIf no improvement in bilirubin then discontinueMathurin P Mathurin P HepatolHepatol

2003;38;1363-92003;38;1363-9

Louvet A Louvet A HepatolHepatol 2008;45:1348-542008;45:1348-54

Page 32: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

PentoxifyllinePentoxifylline

PTX is a phosphodiesterase inhibitor which modulates PTX is a phosphodiesterase inhibitor which modulates the transcription of the TNFthe transcription of the TNFαα-gene, lowers blood -gene, lowers blood viscosity and reduces portal hypertension.viscosity and reduces portal hypertension.

RCT RCT 101 patients with severe alcoholic hepatitis (mDF>32).101 patients with severe alcoholic hepatitis (mDF>32). Given 400mg tds for 28 days vs placeboGiven 400mg tds for 28 days vs placebo Mortality 24% vs 46% at 28 daysMortality 24% vs 46% at 28 days Significant reduction in hepatorenal syndromeSignificant reduction in hepatorenal syndrome

Acriviadis E, Gastro 2000 119;1637-48

Page 33: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

3) ALP Elevated3) ALP Elevated

Cholestatic Illness Cholestatic Illness ((With or without jaundice)With or without jaundice)

Differentiate from Bony ALPDifferentiate from Bony ALP

GGT, ALP iso-enzymesGGT, ALP iso-enzymes

Page 34: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Investigation of CholestasisInvestigation of Cholestasis

Dilated bile ducts

Non-dilated bile ducts

Full liver screen

Raised ALP

Check GT if isolated rise

1) Stop alcohol

2) Stop hepatotoxic drugs

3) Advise weight loss if BMI>25

4) Recheck LFT’s after an interval

Persistently raised ALP

ConsiderMRCPERCP

Other imaging

Diagnosis made-Treat disease

Non diagnostic Ix-consider

Liver biopsy

Page 35: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Liver ALP ElevatedLiver ALP Elevated Cholestatic IllnessCholestatic Illness

AcuteAcute

CBD stones/GallstonesCBD stones/Gallstones Tumours 1Tumours 1ºº or 2 or 2ºº Pancreatic pathologyPancreatic pathology DrugsDrugs InfiltrationInfiltration SODSOD

ChronicChronic

PBCPBC Sclerosing CholangitisSclerosing Cholangitis

• 11ºº or 2 or 2ºº NASHNASH αα-1 antitrypsin-1 antitrypsin SarcoidSarcoid AmyloidAmyloid HIVHIV

Page 36: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

Drug Induced CholestasisDrug Induced Cholestasis Intrahepatic Hepatocellular Cholestasis Intrahepatic Hepatocellular Cholestasis

Intrahepatic Ductular cholestasisIntrahepatic Ductular cholestasis

DuctopenicDuctopenic

GranulomatousGranulomatous

AllopurinolAllopurinolAntithyroid agentsAntithyroid agentsAugmentinAugmentinAzathioprineAzathioprineBarbituratesBarbituratesCaptoprilCaptoprilCarbamezepineCarbamezepineChlorpromazineChlorpromazineChlorpropamideChlorpropamideClindamycinClindamycinClofibrateClofibrateDiltiazemDiltiazemErythromycin estolateErythromycin estolateFlucloxacillinFlucloxacillinIsoniazidIsoniazidLisinoprilLisinoprilMethyltestosteroneMethyltestosteroneOral contraceptives (containing estrogens)Oral contraceptives (containing estrogens)Oral hypoglycemics Oral hypoglycemics PhenytoinPhenytoinTrimethoprim-sulfamethoxazole Trimethoprim-sulfamethoxazole

Page 37: Help with Hepatology Spire 2013 Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust.

The ENDThe END

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